Streptococcus suis serotype 2 is an important porcine bacterial pathogen and an emerging zoonotic agent causing sudden death (pigs), septic shock (humans), and meningitis (both species), with exacerbated inflammation being a hallmark of the infection. A rapid, effective, and balanced innate immune response against S. suis is critical to control bacterial growth and limit the spread of the pathogen without causing excessive inflammation. Even though interleukin (IL)-1 is regarded as one of the most potent and earliest pro-inflammatory mediators produced, its role in the S. suis pathogenesis has not been studied.
Using a well-standardized mouse model of systemic infection, we showed that an intermediately pathogenic sequence type (ST) 25 North American strain, a highly pathogenic ST1 European strain, and the epidemic ST7 Chinese strain induce high levels of IL-1 in important filter organs such as liver and spleen. Moreover, dendritic cells and macrophages, which are two cell types centrally involved in the S. suis pathogenesis, are important sources of this cytokine, with the ST7 strain secreting the highest levels. The study of the underlying mechanisms involved in this production showed that, independently of the strain, IL-1β production required MyD88 and involved recognition via TLR2 and possibly TLR7 and TLR9. This suggests that recognized bacterial components are similar and conserved between S. suis strains. However, very high levels of the pore-forming toxin suilysin produced by the ST7 strain only, are required for efficient maturation of proIL 1β. Such maturation involved the activation of the NLRP3, NLRP1, AIM2, and NLRC4 inflammasomes via pore formation and ion efflux.
Using IL-1R-/- mice, we demonstrated that IL-1 signaling may play a beneficial role during S. suis systemic infection by modulating the inflammation required to control and clear bacterial burden, thus, promoting host survival. Beyond a certain threshold, however, S. suis-induced inflammation cannot be counter-balanced by this signaling, making it difficult to discriminate its role. A better understanding of the underlying mechanisms involved in the control of inflammation could help to develop control measures for this important porcine and zoonotic agent.